Brian Ruyle
Washington University in St Louis, MO·Neuroscience·Early-career
Most opioid overdose deaths now involve fentanyl, a synthetic opioid that is extremely potent and stops breathing within moments, leaving little time to intervene. Research on why opioids suppress breathing has focused mostly on circuits in the lower, front part of the brainstem.
- Fields
Neuroscience
Pharmacology
Physiology
- Topics
fentanyl
opioid-induced respiratory depression
mu opioid receptor
- Grants
- 1 known grant, through Aug 2028
What they work on
- Determine whether fentanyl acts before or after the synapse in the nucleus of the solitary tract, using a new transgenic MOR-Cre rat line with chemogenetics, optogenetics and fiber photometry to manipulate and record mu-opioid-receptor-expressing cells.
- Test how incoming vagus nerve fibers drive catecholaminergic (noradrenaline-releasing) and GABAergic (inhibitory) neurons of the nTS, and how fentanyl disrupts that signaling, using fiber photometry, chemogenetics and immunohistochemistry in transgenic rats.
- Test whether catecholaminergic and GABAergic nTS neurons are necessary for the onset, severity or duration of opioid-induced respiratory depression, by selectively manipulating each population in transgenic rats during intravenous fentanyl exposure.
- Quantify the contribution of mu opioid receptors on noradrenergic cells by measuring breathing and cardiovascular depression in mice in which the receptor has been knocked out of those cells.
More about the research
This project looks at a different region, the nucleus of the solitary tract (nTS), which sits in the back of the brainstem and acts as the brain's main inbox for signals from the body about blood oxygen, blood pressure and lung stretch. The nTS is packed with mu opioid receptors, the protein that opioids act on, yet its contribution to opioid-induced cardiorespiratory depression has barely been tested.
Why it matters
Naloxone rescue often arrives too late with fentanyl. By pinpointing which receptors and neurons in the nucleus of the solitary tract set how fast and how severely breathing fails, this work could identify new targets for drugs that protect or restore cardiorespiratory reflexes during overdose, benefiting people with opioid use disorder and those treated with high-potency opioids.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Glenn M Toney
Texas A&M University-College Station, TX·Neuroscience
Test whether raising the brain's own opioids in the PVH of normal mice reproduces the heightened opioid-induced respiratory depression seen in mice exposed to chronic intermittent hypercapnic hypoxia, a model of sleep apnea.
Jamie Maguire
Tufts University, MA·Neuroscience
Test whether activity in the pathway from stress-hormone CRH neurons in the hypothalamus to the brainstem's nucleus of the solitary tract is increased in chronically epileptic mice at risk of SUDEP.
Thomas Keck
Rowan University, NJ·Pharmacology
Test whether combining morphine with MP-III-024, a compound that enhances α2/α3 GABA-A receptor signaling, gives stronger pain relief without more tolerance, constipation or respiratory depression in preclinical models.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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